We will test the hypothesis that the bioavailability of FK506 in stable renal transplant recipients, under steady state conditions, is largely determined by both enteric and hepatic P450 3A4 activity. Furthermore, the effect of the intestinal multi-drug resistance (mdr1) transporter on enteric metabolism and subsequent FK506 bioavailability will be examined. The underlying hypothesis is that interpatient variation in P450 3A4 and mdr1 expression largely accounts for interindividual differences in the oral clearance of FK506.